Hiroyuki Wakiyama

The Role of Cyclin-dependent Kinase Inhibitor p27 in Squamous Cell Carcinoma of the Esophagus

The level of p27 expression decreases during tumor development and progression. Loss of p27 protein provides independent prognostic information in breast, prostate, colon, stomach and lung carcinomas. We generated a new polyclonal antibody against p27 and carried out immunohistochemical analysis of p27 expression in 61 specimens of esophageal squamous cell carcinoma, 10 carcinoma in situ specimens, and 5 squamous epithelial dysplasia specimens of the esophagus. We examined the correlation of p27 expression with various clinicopathologic features and prognosis. In squamous epithelial dysplasia, the p27-positive cells were located in the superficial normal-appearing cells, not in the atypical cells. In carcinoma in situ, the expression of p27 was markedly lower than in normal esophageal epithelium. In advanced squamous cell carcinomas, high p27 correlated significantly with the degree of differentiation (p = 0.0002) and the depth of tumor invasion (p = 0.001) was statistically significant. The high p27 expression group had a better prognosis than did the low or negative p27 expression groups, but these differences were not statistically significant. These observations may imply that a decrease in p27 expression occurs early on in the carcinogenesis of esophageal carcinoma. In addition, p27 expression may correlate with the histologic differentiation of squamous cell carcinoma of the esophagus.

Therapeutic effect of granulocyte colony‐stimulating factor and cephem antibiotics against experimental infections in neutropenic mice induced by cyclophosphamide

Effects of recombinant human granulocyte colony‐stimulating factor (rhG‐CSF) against severe infections in cyclophosphamide (CY)‐induced neutropenic mice were investigated by its single use or by its combination with cephem antibiotics. Treatment with rhG‐CSF increased the number of peripheral blood leucocytes and strikingly shortened the duration of the neutropenic state. Most of the regained population in the peripheral blood leucocytes were neutrophils. Functions of neutrophils, such as phagocytic activity, superoxide release, and expression of Mac‐1 molecules, were remarkably enhanced by administration of rhG‐CSF. When rhG‐CSF was administered to CY‐induced neulropenic mice before infection, protective effects against various kinds of bacteria were remarkable. On the other hand, such remarkable effects were not observed when rhG‐CSF was administered after infections. However, even in the case of post‐infectious treatment, a combination therapy of rhG‐CSF with cephem antibiotics, particularly with Cefodizime (CDZM), showed a significant improvement in the survival rate and a decrease in the number of viable bacteria in the liver. These results suggest that a combination therapy of rhG‐CSF with cephem antibiotics, especially with CDZM, is an efficient regime against severe infections in patients with ncutropenia induced by a heavy anti‐tumour chemotherapy.